Written by Carol Petersen, RPh, CNP – Women’s International Pharmacy

Research has sought to identify the unique characteristics of hormones for decades. This is difficult, however, because hormones do not act in a vacuum, but have distinct relationships with each other.

Introducing the Hypothalamus, Pituitary Gland and the Adrenal Glands One of the more complicated hormone relationships involves the HPA axis. The HPA axis is a set of interactions and signals that exist between the Hypothalamus, the Pituitary gland and the Adrenal glands. This relationship is an indispensable part of our existence.

The hypothalamus is a very tiny area in the brain with an enormous number of functions. Some of these functions include the regulation of body temperature, hunger, attachment behaviors, thirst, fatigue, sleep, and circadian rhythms. The hypothalamus produces a number of hormones which directly stimulate the pituitary gland.

The pituitary gland is also located in the brain and produces hormones that play a role in regulating the thyroid gland, ovaries, testes, and adrenal glands among other things.

The adrenal glands are located above each kidney and produce hormones that help the body control blood sugar, burn protein and fat, react to stressors like a major illness or injury, and regulate blood pressure.

An example of HPA axis activity (i.e., the interaction between these three glands) is as follows: In response to stress, the hypothalamus produces corticotropic releasing hormone (CRH) which signals the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then signals the adrenal glands to produce stress hormones cortisol, epinephrine, and norepinephrine to be used by the body to respond to the stressor. Uniquely, women experience more stimulation to the HPA axis under conditions of stress than men do.

The HPA Axis is Self-Regulating Not only does the HPA axis work to produce hormones to respond to stress, it also regulates itself so the body stops producing stress hormones when they’re no longer needed. When cortisol is released by the adrenal glands into the blood, receptors in both the hypothalamus and the pituitary gland are able to detect this rise in cortisol. The activation of these receptors turns down the production of CRH and ACTH ultimately resulting in a decrease in the production of cortisol. Ideally, the interaction between the hypothalamus, the pituitary gland, and the adrenal glands creates an environment of stability and consistency using these feedback loops.

Sex Hormones The hypothalamus and the pituitary gland also play a role in regulating the production of sex hormones. The hypothalamus produces gonadotropin releasing hormones (GnRH) which stimulate the pituitary gland to produce luteinizing hormone (LH) and follicle stimulating hormone (FSH) which in turn stimulate the production of estrogens, progesterone, and testosterone by the ovaries and testes. The hypothalamus and the pituitary gland monitor and regulate the ebb and flow of sex hormones with a feedback loop similar to the one used by the HPA axis.

Failure of the HPA Axis Feedback Loop If the body believes it is under constant stress, the hypothalamus and pituitary gland continue to produce CRH and ACTH to stimulate more and more cortisol production. Eventually, however, the system starts to malfunction. Chronic high cortisol levels damage the production of GnRH from the hypothalamus and, as a double whammy, increase the production of a gonadotropin inhibiting hormone (GnIH), which disturbs the production of sex hormones from the ovaries and testes.

What Happens Next? Infertility is a significant consequence of the disruption of the delicate hormone symphony. Continued, elevated levels of cortisol are thought to be a prime cause of infertility:

Stress may increase the production of prolactin from the pituitary gland which can inhibit ovulation.

Cortisol increases inflammation in the uterus which may cause cramping, spasms, and even miscarriage.

Increased spasms may cause damage to the egg in the fallopian tube.

Disruptions of the HPA axis are thought to be an underlying cause of polycystic ovarian syndrome (PCOS), a condition associated with infertility in young women.

Weight gain is another potential consequence when the HPA axis is disrupted:

Ghrelin is a hormone produced in the stomach which contributes to the feeling of hunger. Once food is consumed, ghrelin production is turned off with some help from a neurotransmitter named dopamine. Cortisol can interfere with dopamine activity which may leave one feeling hungry even after eating.

Another hormone called leptin, which is produced in fat cells, inhibits food cravings and initiates fat burning. Cortisol can block the release of leptin. Fat deposited in the abdomen has 30% more cortisol receptors than the rest of the body’s fat, so the cortisol blocking effect on leptin release may be further enhanced in individuals with an excess of abdominal fat.

Cortisol amps up insulin release in response to grains and fruits possibly leading to increased food cravings.

What Can We Do to Reverse This? The most obvious step is to take measures to relieve chronic stress. This can include massage, yoga, meditation, deep breathing, exercise and diet. Natural supplements can also be used. Lactium, a peptide isolated from milk may be used to re-sensitize the hypothalamus to cortisol and re-establish the feedback loop. Herbs like magnolia, ashwaganda, schizandra can moderate cortisol production. Theanine from green tea and the amino acid GABA can also mitigate stress reactions. Judicious use of bioidentical hormones may also help break this cycle of dysfunction.

The takeaway point from Dr. Kendall-Reed’s presentation is that high levels of stress and persistent high levels of cortisol affect the very intricate and complicated balance of many hormones. Learning to manage stress with life style, nutrients, hormones and perception may help restore more balanced functioning to many of the body’s systems.